Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Cell Rep. 2023 Sep 26;42(9):113052. doi: 10.1016/j.celrep.2023.113052. Epub 2023 Sep 1.
Meiotic gene expression in budding yeast is tightly controlled by RNA-binding proteins (RBPs), with the meiosis-specific RBP Rim4 playing a key role in sequestering mid-late meiotic transcripts to prevent premature translation. However, the mechanisms governing assembly and disassembly of the Rim4-mRNA complex, critical for Rim4's function and stability, remain poorly understood. In this study, we unveil regulation of the Rim4 ribonucleoprotein (RNP) complex by the yeast 14-3-3 proteins Bmh1 and Bmh2. These proteins form a Rim4-Bmh1-Bmh2 heterotrimeric complex that expels mRNAs from Rim4 binding. We identify four Bmh1/2 binding sites (BBSs) on Rim4, with two residing within the RNA recognition motifs (RRMs). Phosphorylation and dephosphorylation of serine/threonine (S/T) residues at these BBSs by PKA kinase and Cdc14 phosphatase activities primarily control formation of Rim4-Bmh1/2, regulating Rim4's subcellular distribution, function, and stability. These findings shed light on the intricate post-transcriptional regulatory mechanisms governing meiotic gene expression.
芽殖酵母减数分裂基因表达受 RNA 结合蛋白（RBPs）的严格调控，其中减数分裂特异性 RBP Rim4 在隔离中期晚期减数分裂转录本以防止过早翻译方面发挥关键作用。然而，对于 Rim4-mRNA 复合物的组装和拆卸机制，对于 Rim4 的功能和稳定性至关重要，但仍知之甚少。在这项研究中，我们揭示了酵母 14-3-3 蛋白 Bmh1 和 Bmh2 对 Rim4 核糖核蛋白（RNP）复合物的调节作用。这些蛋白质形成 Rim4-Bmh1-Bmh2 异源三聚体复合物，将 mRNAs 从 Rim4 结合中逐出。我们在 Rim4 上鉴定了四个 Bmh1/2 结合位点（BBS），其中两个位于 RNA 识别基序（RRMs）内。PKA 激酶和 Cdc14 磷酸酶活性对这些 BBS 上丝氨酸/苏氨酸（S/T）残基的磷酸化和去磷酸化主要控制 Rim4-Bmh1/2 的形成，调节 Rim4 的亚细胞分布、功能和稳定性。这些发现揭示了调控减数分裂基因表达的复杂转录后调控机制。
